Impact of bacterial pneumonia and Pneumocystis carinii pneumonia on human immunodeficiency virus disease progression. Pulmonary Complications of HIV Study Group.

The course of pneumonia caused by pyogenic bacteria and Pneumocystis carinii was examined in a multicity cohort study of HIV infection. The median duration of survival among 150 individuals following initial bacterial pneumonia was 24 months, compared with 37 months among 299 human immunodeficiency virus (HIV)-infected control subjects matched by study site and CD4 lymphocyte count (P<.001). For 152 subjects with P. carinii pneumonia, median survival was 23 months, compared with 30 months for 280 matched control subjects (P = .002). Median durations of survival associated with the two types of pneumonia differed by only 47 days, despite a higher median CD4 lymphocyte count associated with bacterial pneumonia. These results suggest that both P. carinii pneumonia and bacterial pneumonia are associated with a significantly worse subsequent HIV disease course. The similarity of prognosis after one episode of bacterial pneumonia vs. an AIDS-defining opportunistic infection and the proportion of cases occurring in association with a CD4 lymphocyte count of >200 suggest that measures to prevent bacterial pneumonia should be emphasized.     

Head-to-Head Evaluation of Five Chlamydia Tests Relative to a Quality-Assured Culture Standard

Nucleic acid amplification tests offer superior sensitivity for the detection of Chlamydia trachomatis infection, but many laboratories still use nonamplification methods because of the lower cost and ease of use. In spite of their availability for more than a decade, few studies have directly compared the nonamplification tests. Such comparisons are still needed in addition to studies that directly compare individual nonamplification and amplification tests. The purpose of this study was to evaluate and compare the performance characteristics relative to culture of five different tests for the detection of C. trachomatis with and without confirmation of positive results. The tests were applied to endocervical specimens from 4,980 women attending family planning clinics in the northwestern United States. The five nonculture tests included Chlamydiazyme (Abbott), MicroTrak direct fluorescent antibody (DFA) (Syva), MicroTrak enzyme immunoassay (EIA) (Syva), Pace 2 (Gen-Probe), and Pathfinder EIA (Sanofi/Kallestad). All positive results obtained with a nonculture test (except MicroTrak DFA) were confirmed by testing the original specimens with a blocking antibody test (Chlamydiazyme), a cytospin DFA (MicroTrak EIA and Pathfinder EIA), and a probe competition assay (Pace 2). The prevalence of culture-proven chlamydia was 3.9%. The sensitivities of the nonculture tests were in a range from 62 to 75%, and significant differences between tests in terms of sensitivity were observed. The positive predictive value for each test was 0.85 or higher. The specificities of the nonculture tests without performance of confirmations were greater than 99%. Performing confirmatory tests eliminated nearly all of the false positives.     

Geographical variation in relationships between parental body size and offspring phenotype at birth

BACKGROUND: Size and body proportions at birth are partly determined by maternal body composition, but most studies of mother-baby relationships have only considered the effects of maternal height and weight on offspring birth weight, and few have examined the size of effects. Paternal size and body composition also play a role, primarily through the fetal genome, although few studies have investigated relationships with neonatal phenotype. METHODS: Data from the UK, Finland, India, Sri Lanka, China, DR Congo, Nigeria and Jamaica were used to investigate the effects of maternal measures (derived at 30 weeks' gestation, n=16,418), and also paternal size (n=3,733) on neonatal phenotype, for singleton, live-born, term births. RESULTS: After accounting for variation in maternal size and shape across populations, differences in neonatal phenotype were markedly reduced. Mother-baby relationships were similar across populations, although some were stronger in developing countries. Maternal height was generally the strongest predictor of neonatal length, maternal head circumference of neonatal head and maternal skinfold thickness of neonatal skinfolds. Relationships with maternal arm muscle area were generally weak. Effects of paternal height and body mass index were weaker than the equivalent maternal measurements in most studies. CONCLUSIONS: Differences in maternal body composition account for a large part of the geographical variation in neonatal phenotype. The size of the effects of all maternal measures on neonatal phenotype suggests that nutrition at every stage of the mother's life cycle may influence fetal growth. Further research is needed into father-baby relationships and the genetic mechanisms that influence fetal growth.     

Unlocking specialists' attitudes toward primary care gatekeepers.

OBJECTIVES: Many managed care plans rely on primary care physicians to act as gatekeepers, which may increase tension between these physicians and specialists. We surveyed specialist physicians in California to determine whether their attitudes toward primary care gatekeepers differed depending on how the specialists were paid and the settings in which they practiced. STUDY DESIGN: We performed a cross-sectional survey using a mailed questionnaire. The predictors of specialist attitudes toward gatekeepers were measured using chi-square, the t test, and regression analyses. POPULATION: A probability sample of 1492 physicians in urban counties in California in the specialties of cardiology, endocrinology, gastroenterology, general surgery, neurology, ophthalmology, and orthopedics was used. OUTCOMES: We used questions about specialists' attitudes toward primary care physicians in the gatekeeper role. A summary score of attitudes was developed. RESULTS: A total of 979 physicians completed the survey (66%). Attitudes toward primary care physicians were mixed. Relative to nonsalaried physicians, those who were salaried had a somewhat more favorable attitude toward gatekeepers (P = .13), as did physicians with a greater percentage of practice income derived from capitation (P =.002). CONCLUSIONS: Specialists' attitudes toward the coordinating role of primary care physicians are influenced by the practice setting in which the specialists work and by financial interests that may be threatened by referral restrictions. Policies that promote alternatives to fee for service and shift specialty practice toward more organized group settings may generate a common sense of purpose among primary care physicians and specialists.     

Tallness and overweight during childhood have opposing effects on breast cancer risk.

Using birth and school health records we studied how weight and height during childhood affect breast cancer risk among 3447 women born during 1924-33 at the University Hospital of Helsinki, Finland. Through linkages with the National Hospital Discharge Registry and the Cause of Death Registry we identified 177 women who during 1971-1995 had been admitted to hospital with breast cancer, of whom 49 had died from the disease. Of these, 135 (76%) were aged 50 years or more at the time of diagnosis, and therefore likely to have been post-menopausal. Hazard ratios for breast cancer rose with increasing weight and length at birth, though neither trend was statistically significant. At each age, from 7 to 15 years, the girls who later developed breast cancer were on average taller and had lower body mass than the other girls. Unadjusted hazard ratios rose across the range of height (P = 0.01 at age 7 years) and fell across the range of body mass index (P = 0.009 at age 7 years). In a simultaneous analysis the hazard ratio for breast cancer was 1.27 (95% CI 0.97-1.78, P = 0.08) for every kilogram increase in birth weight and 1.21 (95% CI 1.06-1.38, P = 0.004) for every kg/m(2) decrease in body mass index at 7. Our findings indicate that tallness in childhood is associated with increased risk of developing breast cancer. One possible explanation is persisting high plasma concentrations of insulin-like growth factors in tall women. In contrast, we found that being overweight in childhood reduces breast cancer risk. The increased adipose tissue-derived oestrogen levels in overweight children could induce early breast differentiation and eliminate some targets for malignant transformation.     

Suppressed apoptosis of pre-B cells in bone marrow of pre-leukemic p190bcr/abl transgenic mice.

Mice transgenic for a p190bcr/abl construct develop pre-B cell leukemia/lymphoma, providing a model of Ph+ ALL. To investigate events in tumorigenesis, immunofluorescence labeling, flow cytometry and a short-term culture assay were used to quantitate precursor B cells and their apoptotic rates in bone marrow of p190bcr/abl transgenic mice over a wide age range. Malignancies appeared rapidly at 8-12 weeks of age, followed by slower tumor onset. At 8-12 weeks in normal mice, the apoptotic rate fell among pro-B cells but increased steeply among pre-B cells, while the total number of B lineage cells declined. In contrast, in p190bcr/abl transgenic mice over the same time period, while pro-B cells remained normal in apoptotic rate and number, apoptosis of pre-B cells was markedly inhibited and the number of B lymphocytes increased. At later ages (14-30 weeks), B cell precursors in control mice remained constant in apoptotic activity and number, while in the few surviving transgenic mice B cell populations were expanded. The results reveal characteristic changes in apoptotic activity among B cell precursors in bone marrow during early life, severely perturbed in preleukemic p190bcr/abl transgenic mice by a preferential suppression of pre-B cell apoptosis. p190bcr/abl may thus promote leukemogenesis by permitting aberrant cells generated during early B cell development to evade a normal quality checkpoint and negative selection.